The long-term research goal is to determine the relation of plasma sex hormone levels to androgen action. The amount of hormone delivered to the hormone-active site is proportional to the free (unbound) plasma hormone concentration. Thus, androgen action is related to the free androgen level. At equilibrium, the free androgen level is determined by the concentrations of testosterone, other androgenic 17Beta- hydroxysteroids (most of which were previously unrecognized), and "testosterone binding globulin". The free androgen level is also dependent on dynamic factors, the rates of androgen secretion and metabolism. Another determinant of androgen action is the plasma concentration of anti-androgens, for example, estradiol. Estradiol competes for binding sites on testosterone binding globulin; hence, increased androgen levels result in increased free estradiol. The proposed research is designed to quantitate the interrelationship between androgen and estrogen binding and to determine the sources and secretion rate of non-testosterone androgens. The specific aims of the proposed research are, therefore, 1) to develop methods to measure the free fraction of each androgen in plasma, 2) to develop methods to measure plasma androst-5-en-3Beta, 17Beta-diol and the 5alpha-androstan-3alpha/Beta, 17Beta-diols, 3) to determine the source and secretion rate of these androgens and their relation to testosterone, 4) to develop a method for the measurement of free plasma estradiol, 5) to determine the factors which influence the effective level of testosterone binding globulin, and 6) to seek improved understanding of normal and abnormal sexual development. Binding protein and hormone levels will be measured by radiostereoassay methods. Steroid intermediary metabolism will be studied by constant infusion isotopic techniques.